Bacteriophobic Coatings for Inhibition of Pathogenic Biofilms This proposal describes the preparation, characterization, and evaluation of functional coatings for the inhibition of bacterial cell colonization and biofilm formation on orthopaedic implants. Bacterial infections are the second most commonly attributed cause of implant failure. Such infections, which become established on plates, rods, screws and pins, necessitate prolonged antibiotic treatment and/or removal of the implant with multiple washout/debridement procedures to eradicate the infection, followed by implantation of a new device. This treatment is associated with high patient morbidity, loss of function, and significant health care costs. To address this need, bacteria repellant coatings are proposed that function as a physical barrier to bacterial cell attachment or as bioactive moieties to disrupt the bacterial membrane. A prototypical coating that inhibits bacteria colonization has been designed, synthesized, and evaluated. A detailed, systematic investigation is proposed that encompasses the following specific aims for this four-year proposal: Aim 1. Identify peptides that bind to titanium using phage display and measure the binding affinity and selectivity of these peptides to titanium. Aim 2. Synthesize and characterize functional multivalent bacteriophobic coatings. Aim 3. Characterize biofilm inhibition in vitro and ex vivo on titanium with and without the bacteriophobic coating. Aim 4. Demonstrate reduction of perioperative infection rates in vivo. The results of successful completion of this study will be: 1) identification of one or more bacteriophobic coatings;2) understanding of the advantages and limitations of this strategy to reduce the rate of implant infection;3) identification of potential design variations for improved performance;4) demonstration of a new approach that may lessen the use of antibiotics and the resulting clinical challenges associate with treating antibiotic resistant pathogens;and 5) contributions to the design and engineering of future bacteriophobic coatings that possess specific physical properties or biological activities for a variety of implant metals. PUBLIC HEALTH RELEVANCE The current treatment for implant-associated infections includes prolonged antibiotic treatment and/or replacement of the infected implant. This treatment is less than ideal, and innovative strategies to prevent bacterial colonization on medical devices are needed. This proposal addresses this national health need through development and evaluation of new coatings that prevent implant associated infections.